Radiotherapy upregulated immune checkpoints contribute to the development of second primary OSCC

Radiation may upregulate ICs expression in oral mucosa and contribute to the development of s-OSCC.

Clinical specimens of second primary oral squamous cell carcinoma after radiotherapy (s-OSCC) and primary OSCC (p-OSCC) were collected. The expression and prognostic value of PD-1, VISTA, and TIM-3 were analyzed using immunohistochemistry. To further clarify the relationship between radiation and ICs alteration, a rat model was constructed to explore the spatiotemporal changes of ICs in the oral mucosa after radiation.

In carcinoma tissue, the expression of TIM-3 was higher in s-OSCC than in p-OSCC, while the expression of PD-1 and VISTA was similar between the groups. In para-carcinoma tissue, the expression of PD-1, VISTA, and TIM-3 was higher in s-OSCC. High ICs expression was associated with poor survival. In the rat model, ICs were locally upregulated in the irradiated tongue. Moreover, there was a bystander effect, in which the ICs were also upregulated in the unirradiated site.